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Proteases Structure And Function

Author : Klaudia Brix
ISBN : 9783709108857
Genre : Science
File Size : 50.14 MB
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Proteolysis is an irreversible posttranslational modification affecting each and every protein from its biosynthesis to its degradation. Limited proteolysis regulates targeting and activity throughout the lifetime of proteins. Balancing proteolysis is therefore crucial for physiological homeostasis. Control mechanisms include proteolytic maturation of zymogens resulting in active proteases and the shut down of proteolysis by counteracting endogenous protease inhibitors. Beyond the protein level, proteolytic enzymes are involved in key decisions during development that determine life and death – from single cells to adult individuals. In particular, we are becoming aware of the subtle role that proteases play in signaling events within proteolysis networks, in which the enzymes act synergistically and form alliances in a web-like fashion. Proteases come in different flavors. At least five families of mechanistically distinct enzymes and even more inhibitor families are known to date, many family members are still to be studied in detail. We have learned a lot about the diversity of the about 600 proteases in the human genome and begin to understand their physiological roles in the degradome. However, there are still many open questions regarding their actions in pathophysiology. It is in this area where the development of small molecule inhibitors as therapeutic agents is extremely promising. Approaching proteolysis as the most important, irreversible post-translational protein modification essentially requires an integrated effort of complementary research disciplines. In fact, proteolytic enzymes seem as diverse as the scientists working with these intriguing proteins. This book reflects the efforts of many in this exciting field of research where team and network formations are essential to move ahead.
Category: Science

Structure Function Relationships Of Proteolytic Enzymes

Author : P. Desnuelle
ISBN : 9781483261171
Genre : Science
File Size : 20.20 MB
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Structure–Function Relationships of Proteolytic Enzymes provides information pertinent to the fundamental aspects of proteolytic enzymes. This book presents the historical role of proteolytic enzyme as a group in protein and enzyme chemistry. Organized into 23 chapters, this book begins with an overview of the results obtained from investigation on the chymotrypsinogens of porcine origin. This text then examines the differences of amino acid sequence between chymotrypsin, trypsin, and elastase that affect the substrate binding site, which reflect the specificity differences between these enzymes. Other chapters consider the kinetic parameters related to the trypsin-catalyzed hydrolysis of several model peptides. This book discusses as well the acetylation of trypsin, which result in functional consequences varying from complete inactivation to promotion of activity. The final chapter deals with the physical properties of stem bromelain in comparison with the data for three other sulfhydryl proteases of plant origin. This book is a valuable resource for enzymologists, microbiologists, and biochemists.
Category: Science

Acid Proteases Structure Function And Biology

Author : Jordan Tang
ISBN : 9781475707199
Genre : Science
File Size : 53.36 MB
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In the past ten years, a number of proceedings of symposia on the structure and function of proteolytic enzymes have been pub lished. Their coverage of acid proteases has been limited, mainly due to the lack of significant new information on the structure of these enzymes. In the last four years, however, the primary and tertiary structures of a number of acid proteases have been deter mined, prompting the need to discuss the meanings of the old data and the possibilities for new experimentations. It was for this purpose that the "Conference on Acid Proteases: Structure, Function, and Biology" was organized. It took place at the University of Oklahoma on November 21-24, 1976. This book is a collection of the main lectures delivered at the Conference. Acid Proteases, by definition refers to a group of proteases having an optimal pH in acidic solutions. The classic examples are pepsin and chymosin. Some catalytic features are obviously shared by these proteases, most notably, their inhibition by pepstatin. The use of active center-directed inactivators such as diazoacetyl norleucine methyl ester and 1,2-epoxy-3-(p-nitrophenoxy)propane has shown that two catalytic aspartyl residues are present in most of these enzymes. These apparent cornmon features have prompted the suggestion by several investigators to name this group of enzymes "aspartyl proteases" or "carboxyl proteases".
Category: Science

Viral Proteases And Their Inhibitors

Author : Satya Prakash Gupta
ISBN : 9780128096826
Genre : Science
File Size : 20.49 MB
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Viral Proteases and Their Inhibitors provides a thorough examination of viral proteases from their molecular components, to therapeutic applications. As information on three dimensional structures and biological functions of these viral proteases become known, unexpected protein folds and unique mechanisms of proteolysis are realized. This book investigates how this facilitates the design and development of potent antiviral agents used against life-threatening viruses. Users will find descriptions of each virus that detail the structure and function of viral proteases, discuss the design and development of inhibitors, and analyze the structure-activity relationships of inhibitors. This book is ideal biochemists, virologists and those working on antiviral agents. Provides comprehensive, state-of-the-art coverage of virus infections, the virus lifecycle, and mechanisms of protease inhibition Analyzes structure-activity relationships of inhibitors of each viral protease Presents an in-depth view of the structure and function of viral proteases
Category: Science

Aspartic Acid Proteases As Therapeutic Targets

Author : Arun K. Ghosh
ISBN : 9783527641628
Genre : Medical
File Size : 88.26 MB
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In this ground-breaking practical reference, the family of aspartic acid proteases is described from a drug developer's perspective. The first part provides a general introduction to the family of aspartic acid proteases, their physiological functions, molecular structure and inhibition. Parts two to five present various case studies of successful protease inhibitor drug design and development, as well as current and potential uses of such inhibitors in pharmaceutical medicine, covering the major therapeutic targets HIV-1 protease, renin, beta-secretase, gamma-secretase,plasmepsins and fungal proteases. A ready reference aimed primarily at professionals in the pharmaceutical industry, as well as for anyone studying proteases and their function.
Category: Medical

Regulatory Proteolytic Enzymes And Their Inhibitors

Author : Staffan Magnusson
ISBN : 9781483153896
Genre : Science
File Size : 78.99 MB
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Regulatory Proteolytic Enzymes and Their Inhibitors consists of contributed papers from the 11th Meeting of the Federation of European Biochemical Societies in Copenhagen in 1977. This collection describes the role of proteases in the physiological regulation, a matter of the activation and de-activation of enzymes. The text also discusses the activation mechanism of pepsinogen and other acid protease zymogens. One paper reviews a discovery — that of a separate and distinct class of precursors, the pre-secretary proteins, and then discusses other studies on preproinsulin. The text then discusses the primary structures and presumed functions of immunoglobulin precursors. Another paper continues with the work of Reich and co-workers who found that transformation of cultured fibroblasts from different species by oncogenic viruses is related to the production and release of proteases that are responsible in activating the proenzyme plasminogen into plasmin. Another paper discusses plasminogen activation as having some relationship with pathological processes. The book also reviews the plasminogen activator secretion by normal and neoplastic human tissues. The text discusses the results when primary cultures established from biopsies of normal kidneys secreted plasminogen activators in amounts over those secreted by actual malignant tissues. The book then notes the role of neutral and acid proteinases in male reproduction and the role of plasminogen activators in female ovulation. This collection can be useful for micro-biologists, research biologists, molecular scientists, and students of molecular biology.
Category: Science

Mechanisms Of Protease Action

Author : Laszlo Polgar
ISBN : 0849369010
Genre : Medical
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A uniform treatment of the four protease groups and a discussion of the differences and similarities in their action is presented in this important new publication. Serine, cysteine, aspartate, and zinc proteases are systematically discussed by nomenclature, evolution, specificity and their regulatory role. The chemistry of the peptide bond, including the catalysis of ester and peptide hydrolyses, is explained. For each protease group the emphasis is placed on the structure and function. Kinetics, enzyme modifications, isotope effects, subzero temperature investigations, nuclear magnetic resonance measurements, X-ray diffraction data, binding of transition-state analogs, zymogen activation, and site-specific mutagenesis are combined to rationalize the action of proteases. Both natural and synthetic inhibitors are considered because of their importance in mechanistic studies and drug design.
Category: Medical

Proteases In Physiology And Pathology

Author : Sajal Chakraborti
ISBN : 9789811025136
Genre : Medical
File Size : 83.81 MB
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Using a multidisciplinary approach, this book describes the biochemical mechanisms associated with dysregulation of proteases and the resulting pathophysiological consequences. It highlights the role and regulation of different types of proteases as well as their synthetic and endogenous inhibitors. The role of proteases was initially thought to be limited to general metabolic digestion. However, we now know that the role of protein breakdown is much more complex, and proteases have multiple functions: they are coupled to turnover and can affect protein composition, function and synthesis. In addition to eliminating abnormal proteins, breakdown has many modulatory functions, including activating and inactivating enzymes, modulating membrane function, altering receptor channel properties, affecting transcription and cell cycles and forming active peptides. The ubiquity of proteases in nature makes them an important target for drug development. This in-depth, comprehensive is a valuable resource for researchers involved in identifying new targets for drug development. With its multidisciplinary scope, it bridges the gap between fundamental and translational research in the biomedical and pharmaceutical industries, making it thought-provoking reading for scientists in the field.
Category: Medical

Retroviral Proteases

Author : Lawrence C. Kuo
ISBN : 0121821420
Genre : Medical
File Size : 57.81 MB
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Methods included in this volume apply to the expression and characterization of retroviral proteases and their inhibitor/substrate design.
Category: Medical

Hydrolytic Enzymes

Author : K. Brocklehurst
ISBN : 9780080860756
Genre : Science
File Size : 20.64 MB
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This newest volume in the impressive New Comprehensive Biochemistry series presents up-to-date discussions of six types of hydrolytic enzyme that are well characterized structurally: aspartic-, cysteins-, and serine-proteinases, carboxypeptidase A, pancreatic ribonuclease A, and the phosphomonoesterases. The emphasis is on molecular mechanisms deduced by crystallographic, kinetic, spectroscopic and molecular genetic studies. The chapters on the various types of proteinases are complemented by others on proteinase inhibitors and intracellular proteolysis. This book will prove valuable to researchers in general biochemistry, particularly those with interest in enzyme mechanism and protein chemistry, and to Honours and Postgraduate students.
Category: Science